This program project is designed to integrate and bring into closer interaction, investigators in different disciplines who are interested in allergic diseases and certain related autoimmune diseases. The main focus is to clarify mechanisms of disease induction, using pharmacological, biochemical and immunological approaches. The program project is divided into six areas. Project I proposes to examine the relationship of the Hageman factor (contact) system and the development of provoked bronchospasm in patients with asthma and allergic and non-allergic bronchitis. This is based on previous evidence that the contact system can be activated by allergic reactions both in vitro and in vivo. Project II is designed to examine the release of leukotriene C and D by human peripheral blood monocytes from patients with atopic disorders and those with aspirin-induced asthma. Factors which regulate the release of leukotrienes, including drugs and mitogen-activated cells will be examined. Project III is designed to study the mechanisms which lead to the induction of asthma by sulfiting agents such as bisulfite, sulfite and metabisulfite. These sulfiting agents are used extensively as preservatives, anti-oxidants and sanitizing agents. The incidence of sulfite sensitivity, mechanisms of induction and treatment modalities will be studied. Project IV will examine the mechanisms of disease induction in angioedema. The specific objective will be to determine the relationship of complement activation with activation of Hageman factor (contact) system leading to the generation of kinin activity which was demonstrated previously. Project V will explore the mechanism by which a polyclonal B cell activator such as Epstein-Barr virus (EBV) may contribute to polyclonal anti-body production which characterizes patients with rheumatoid arthritis, systemic lupus erythematosus, and the hyper-IgE syndromes. Project VI will study the mechanisms whereby certain drugs such as procainamide induce an autoimmune lupus-like syndrome. The predominant autoantibody is anti-histone and studies will be focused on the mechanism of induction and the pathogenic potential of this antigen-antibody system.